Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes

J Clin Endocrinol Metab. 2005 Jun;90(6):3629-37. doi: 10.1210/jc.2004-1942. Epub 2005 Mar 29.


The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine
  • Amino Acid Substitution*
  • Body Mass Index
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Variation*
  • Glutamine
  • Humans
  • Lysine
  • Male
  • Middle Aged
  • Mutation, Missense*
  • PPAR gamma / genetics*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Proline
  • Risk Factors


  • Kir6.2 channel
  • PPAR gamma
  • Potassium Channels, Inwardly Rectifying
  • Glutamine
  • Proline
  • Lysine
  • Alanine